A Predictive Autoantibody Signature in Multiple Sclerosis.

Autor: Zamecnik CR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Sowa GM; Department of Medicine, McGaw Medical Center of Northwestern University, Chicago, IL, USA., Abdelhak A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Dandekar R; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Bair RD; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Wade KJ; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Bartley CM; UCSF Weill Institute for Neurosciences, Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA., Tubati A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Gomez R; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Fouassier C; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Gerungan C; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Alexander J; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Wapniarski AE; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Loudermilk RP; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Eggers EL; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Zorn KC; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA., Ananth K; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Jabassini N; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Mann SA; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA., Ragan NR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Santaniello A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Henry RG; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Baranzini SE; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Zamvil SS; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Bove RM; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Guo CY; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Gelfand JM; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Cuneo R; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., von Büdingen HC; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Oksenberg JR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Cree BA; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Hollenbach JA; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA.; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA USA., Green AJ; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Hauser SL; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA., Wallin MT; Veterans Affairs, Multiple Sclerosis Center of Excellence, Washington, DC and University of Maryland School of Medicine, Baltimore, MD, USA., DeRisi JL; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.; Chan Zuckerberg Biohub, San Francisco, CA, USA., Wilson MR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2023 May 15. Date of Electronic Publication: 2023 May 15.
DOI: 10.1101/2023.05.01.23288943
Abstrakt: Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. Here, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster of PwMS that share an autoantibody signature against a common motif that has similarity with many human pathogens. These patients exhibit antibody reactivity years before developing MS symptoms and have higher levels of serum neurofilament light (sNfL) compared to other PwMS. Furthermore, this profile is preserved over time, providing molecular evidence for an immunologically active prodromal period years before clinical onset. This autoantibody reactivity was validated in samples from a separate incident MS cohort in both cerebrospinal fluid (CSF) and serum, where it is highly specific for patients eventually diagnosed with MS. This signature is a starting point for further immunological characterization of this MS patient subset and may be clinically useful as an antigen-specific biomarker for high-risk patients with clinically- or radiologically-isolated neuroinflammatory syndromes.
Databáze: MEDLINE